When Using DOPPS Slides Modifying DOPPS data, analyses, tables, and graphics in any form is not permitted without prior approval from the DOPPS coordinating center staff. Each DOPPS slide used must include the citation of the associated publication and feature the corresponding DOPPS logo.

DOPPS Slide Use Guidelines Modifying DOPPS data, analyses, tables, and graphics in any form is not permitted without prior approval from the DOPPS coordinating center staff. Each DOPPS slide used must include the citation of the associated publication and feature the corresponding DOPPS logo.

Hypercalcaemia is associated with poor mental health in haemodialysis patients: results from Japan DOPPS The Dialysis Outcomes and Practice Patterns Study (DOPPS) reported high incidence of depression in haemodialysis patients. Hypercalcaemia and high parathyroid hormone (PTH) levels are aetiological factors of psychological disorders. We examined the association between mineral metabolism abnormalities and mental health in Japanese-DOPPS patients. Using baseline data of Japan-DOPPS, Phase 1 (2755 patients, 1999–2001) and Phase 2 (2286 patients, 2002–03), we analyzed mental health using the mental health domain of SF-36. We examined the association between serum corrected calcium, phosphorus, calcium*phosphorus product and intact PTH concentrations, and mental health using analysis of covariance and also the associations between corrected calcium levels and current use of vitamin D and calcium-containing phosphate binder.

Methods We used baseline data of Japan-DOPPS, Phase 1 (2755 patients, 1999–2001) and Phase 2 (2286 patients, 2002–03). The outcome variable was mental health using the mental health domain of SF-36. We examined the association between serum corrected calcium, phosphorus, calciumphosphorus product and intact PTH concentrations, and mental health using analysis of covariance and also the associations between corrected calcium levels and current use of vitamin D and calcium-containing phosphate binder.

KDQOL SF-36 The Japanese version of patient self-reported, health-related quality of life (QOL) questionnaire (SF-36 Health Survey, hereafter SF-36) was distributed to patients for response. The SF-36 is a QOL scale that permits quantitative evaluation of subjective health status and its impact on daily function and social function. The SF-36 consists of 36 questions and when all questions are answered, a score ranging from 0 to100 is calculated for each of the eight domains (e.g. physical function, mental health, social function, role-physical, role-emotional, bodily pain, general health and vitality). A low mental health score represents poor mental health. Patients who were unable to complete the questionnaire, such as those with ostensible cognitive deficits, were excluded.

Analysis Methods Results are expressed as mean +/- SD unless otherwise stated. We examined the correlations between mental health scales and serum corrected calcium, phosphorus and intact PTH concentrations. In this study, pooled data from Phase 1 and Phase 2 studies from Japan-DOPPS were analysed. Based on the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines, serum corrected calcium, phosphorus and intact PTH concentrations were categorized by the following cut-off concentrations: serum corrected calcium: 8.4, 10.2 and 11.0 mg/dl, phosphorus: 2.5, 3.5 and 5.5 mg/dl, and intact PTH: 150, 300 and 600 pg/ml. Cut-off points of Ca*P product were defined based on 25, 50 and 75 percentiles of Ca*P product levels. First, we examined the correlations between corrected calcium, phosphorus, intact PTH concentrations and Ca*P product levels, with mental health scores from the SF-36 using analysis of variance (crude analysis). Then, analysis of covariance was used to examine the associations with adjustment variables. In this analysis, independent variables in the multivariate model were the following: corrected calcium, phosphorus, intact PTH concentrations, sex, age, duration of dialysis, serum albumin, haemoglobin, use/non-use of vitamin D preparation, use/ non-use of calcium-containing phosphate binder, presence/ absence of comorbidity (13 variables) and history of PTX. When the association between Ca*P product level and mental health was examined, the independent variables in the multivariate model were Ca*P product level, intact PTH concentrations, sex, age, serum albumin, haemoglobin, use/ non-use of vitamin D preparation, use/non-use of calciumcontaining phosphate binder, presence/absence of comorbidity (13 variables) and history of PTX.

Table 1. Percentage of patients using vitamin D or calcium-containing phosphate binder categorized by corrected calcium levels Table 1 shows the distribution of patients categorized by corrected calcium levels according to the use/non-use of intravenous vitamin D or its analogue for control of PTH and calcium-containing phosphate binder within one week of the investigation date. The percentage of patients receiving intravenous active vitamin D preparations or calcium-containing phosphate binder was significantly higher in dialysis patients with hypercalcaemia than those without (P<0.0001).

Table 2. Baseline Characteristics (1) The mean age of 4115 patients of Phase 1 and 2 studies was 58.2 +/- 12.4 and 60.9 +/- 12.9 years, respectively, and males formed 63 and 61%, respectively, of the population.

Table 2. Baseline Characteristics (2) The duration of dialysis was less than 6 months in 757 patients. Furthermore, 58% of the patients used vitamin D preparations and 79% used calcium-containing phosphate binders.

Table 2. Baseline Characteristics (3) Hypertension and diabetes were the most commonly observed comorbid conditions among this population of HD patients.

Table 2. Baseline Characteristics (4) Serum concentrations of albumin, calcium, phosphorus and PTH remained relatively constant between the first and second phases of DOPPS.

Association between mental health (MH) score of the SF-36 Health Survey and (A) serum corrected calcium and (B) phosphorus As shown in Figure 1A, 64.0% of patients had the target serum calcium levels, 15.4% had less, and 20.6% had more than that. The mean mental health scores of the group with corrected calcium levels <8.4 mg/dl, 8.4 to <10.2 mg/dl, 10.2 to <11.0 mg/dl and 11.0 mg/dl were 64.1 [95% confidence interval (CI): 62.2–66.1], 64.3 (95%CI: 63.4–65.2), 65.6 (95%CI: 63.6–67.6) and 58.9 (55.9–61.9), respectively. The group with corrected calcium levels 11 mg/dl had a significantly lower mental health score than that with <8.4 mg/dl. The difference was 5.2 points (P¼0.04) and its effects size (ES) was 0.22. Similarly, the group with corrected calcium levels 11 mg/dl had a significantly lower mental health score than that with levels 8.4 to <10.2 mg/dl, and the group with 10.2 to <11.0 mg/dl. The differences were 5.4 points (P¼0.009) and 6.7 points (P¼0.003), respectively, and their ESs were 0.25 and 0.31, respectively. Furthermore, 40.8% of patients had the target serum phosphorus levels, 6.0% had less and 53.2% had more than the target (Figure 1B). There were no associations between serum phosphorus and mental health by crude analysis.

Association between mental health (MH) score of the SF-36 Health Survey and (C) parathyroid hormone (PTH) concentrations and (D) Ca x P product As shown in Figure 1C, 26.1% of patients had target serum intact PTH levels, 51.4% had less and 19.5% had more than the target. There were no associations between serum intact PTH and CaP product and mental health by crude analysis (Figure 1C–D).

Table 3. Differences in mental health score between serum corrected calcium levels by multiple comparison After adjustment for age, sex, serum albumin concentration, haemoglobin, serum phosphorus concentration, use/non-use of vitamin D preparation, use/non-use of calcium-containing phosphate binder, presence/absence of comorbidity (13 variables) and history of PTX, the differences between the group with corrected calcium levels 11.0 mg/dl and groups with 8.4 to <10.2 mg/dl and 10.2 to <11.0 mg/dl were significant. That is, the mental health score of patients with corrected calcium levels of 11.0 mg/dl was 5.0 (95% CI: 0.5–9.6) points lower than that of the group with 8.4 to <10.2 mg/dl and 6.7 (95% CI: 1.6–11.8) points lower than the group with 10.2 to <11.0 mg/dl.

Conclusion In this study, we found a possible association between hypercalcaemia and poor mental health in dialysis patients. Our study also shows that treatment with intravenous active vitamin D preparations and/or oral calcium salts is responsible for the development of hypercalcaemia in dialysis patients. While a cause– effect relationship between hypercalcaemia and deterioration of mental health needs further confirmation through longitudinal studies as well as prospective randomized studies, our observational findings suggest the importance of control of serum calcium concentration in dialysis patients treated with active vitamin D preparations or calcium salts.